R e v is t a d a S o c i e d a d e B r as ile ir a d e M e d ic in a T r o p ic al 2 8 ( 4 ) : 3 3 9 - 3 4 3 , o u t - d e z , 1 9 9 5 .
CLIN ICA L A N D EPID EM IO LO G ICA L FIN D IN G S D URIN G A
M EA SLES O UTBREA K O CCURRIN G IN A PO PULA TIO N
W ITH A fflG H V A CCIN A TIO N CO V ERA G E
Solange A rtim os de O liveira, W alquíria N ascim ento Soares, M arcos O livier D alston, M aria Teresa G.N. de A lmeida and A ntonio Jo sé L. Costa
Fro m M arch 1991 to A pril 1992, 2 5 0 measles suspected cases w ere studied in the M unicipality o f Niterói, State o f Rio de Janeiro . The m edian age fo u n d w as 11 y ears and 76.0% o f the cases w ere in scho o l age children. Expo sure histories w ere present in 1 4 9 patients a nd scho ols w ere the most freq uent sites o f transmission (45.0% ). Vaccinatio n status w as kno w n f o r 1 2 7 studied cases and 76.4% o f them had receiv ed measles v accine befo re their firs t birthday . O ne o r m o re co mplicatio ns w ere repo rted f o r 6 8 cases aitd in 8.9% o f the studied cases hospitalization w as required. Frequency o f co mplications v aried acco rding to each age gro up studied and w ere m o re co mmo nly enco unt ered am o ng children < 1 y ear o f age (55.6% ). The history o f prev io us v accinatio n did not diminish the num ber o f co mplications o f the cases studied. The results o f this w ork show changes in age distributio n o f measles leading to sizeable o utbreaks am o ng teenagers a nd y o ung adults.
Key - w ords: M easles epidemiology . Vaccine failure. M easles co mplicatio ns.
In co untries w here m easles v accinatio n has reached high lev els so m e chang es in d isease ep id em io lo g y hav e b een o bserv ed , and am o ng them , a p ro gressiv e up w ard shift in the age d istributio n o f m easles incid ence to w ard s o ld er child ren820. This increase in the m ean age o f o c c u rre n c e o f m e asle s c ase s is related to p o p ulatio n v accinatio n co v erag e levels. Recently, many autho rs have rep o rted m easles o u tb reak s in te e n ag e rs and ad u lts, and in so m e cases inclu d ing p eo p le p rev io usly vaccinated 71114 22.
D esp ite the d ifferences fo u nd in the
v acc in atio n co v erag e levels am o ng the States
o f Brazil, the num ber o f m easles no tified cases in recent ep id em ics did no t reach the same lev els o bserv ed in the 70’s. This fact is d ue to the pro gressiv e increase in the v accinatio n co v erag e lev els in the last years and the im p act
D isc ip lin a d e D o e n ç a s In f e c c io s a s e Parasitárias d a U niv ersid ad e Fe d eral Flu m in en se, N iteró i, RJ e Fu nd ação M u n ic ip al d e Saú d e d e N ite ró i, RJ, Brasil.
S u p p o r t e d b y C N P q g r a n t n ° 5 0 1 8 4 0 / 9 1 - 5 a n d PRO PP/ U niv ersid ad e Fed eral Flu m in en se.
A d d r e s s t a. D r* So lang e A rtim o s d e O liv eira. D iscip lin a d e D o e n ç as In f e c c io sas e Parasitárias, H o sp ital U niv ersitário A n to n io P e d ro . R . M a rq u ê s d o P aran á 30 3 / 2 ° an d ar, 2 4 0 3 3 - 2 1 0 N ite ró i,R J,Brasil,Fax : ( 0 2 1 ) 717-4459- R e c e b id o p ara p u b lic aç ão e m 10/ 02/ 95.
o f v accinatio n cam p aigns o n the incid ence o f the d isease513.
Until 1984 the ep id em io lo g y o f m easles in the M unicipality o f N iteró i, State o f Rio de Janeiro , w as characterized by high m o rbid ity and mo rtality rates, mainly rep o rted in child ren u n d er fiv e. Sin c e 1985, fo llo w in g the in tro d u c tio n o f n atio n al im m u n iz atio n cam p aigns mainly d irected to child ren 9 - 2 3 m o nths o f ag e, m easles in cid ence and mo rtality have d eclined rapid ly. Ho w ever, it has b een o bserv ed that the m ean ag e o f rep o rted cases increased each y ear5.
M easles incid ence in N iteró i b eg an to increase during the 90’s, but at this tim e m o st o f the cases w ere o bserv ed in child ren fro m 10 to 14 years o f age, fo llo w ed by tho se fro m 5 to 9 y ears o f age. A ltho ugh the ag e gro up at the highest risk co ntinues to b e child ren o f less than o ne year o f age, an increase in the p ro p o rtio n o f m easles cases has o ccurred in o ld er child ren5. A similar p icture has b een d escribed by o ther autho rs, mainly in co untries that hav e achiev ed and su stained hig h co v erage rates71114 ” .
O liv e ir a SA , S o ar e s W N, D als t o n M O , A lm e i d a M TG N , C o s t a A JL. C l in ic al a n d e p id e m i o l o g i c a l f i n d i n g s d u r in g a m e a s le s o u t b r e a k o c c u r in g in a p o p u l a t i o n w it h a h ig h v a c c in a t io n c o v e r ag e . R e v is t a d a S o c i e d a d e B r a s ile ir a d e M e d ic in a T r o p ic al 2 8 : 3 3 9 - 3 4 3 , o u t - d e z , 1 9 9 5 .
MATERIAL AND METHODS
S t u d y d e s ig n . The study w as co nd ucted in N iteró i, State o f Rio d e Janeiro , Brazil. Fro m M arch 1991 to A p ril 1992 an intensiv e surv eillance system w as instituted by the D iv isio n o f Ep id e m io lo g y o f N iteró i D ep artm ent o f H ealth. Phy sicians w ere required to rep o rt susp ected m easles cases immed iately, based o n the criteria established by the Centers fo r D iseases Co ntro l4 as a clinical case: an illness characterized by fev er > 38.3°C, g eneralized m aculo p ap ular rash o f a 3 d ays-d uratio n and, at least o ne o f the fo llo w ing : co ugh, co ryza o r co njunctiv itis. Each case rep o rted to the Dep artm ent o f H ealth w as fo llo w e d up b y a rev ie w o f th e c a s e re c o rd an d in v e stig ate d b y ep id em io lo gists o r nurses o f the D ep artm ent o f Health esp ecially trained to co nfirm clinical d iagno sis. In o rd er to find ad d itio nal cases all health w o rkers w ere instructed to ask patients ab o u t the p resen ce o f rash-like illness o ccurring in their neig hbo urho o d as w ell as am o ng scho o l co lleagues.
A questio nnaire co ntaining the p erso nal d ata, s ig n s an d sy m p to m s o f m e a s le s , v accinatio n histo ry, setting o f transmissio n, and co m p licatio ns w as d esig ned fo r the study. O nly p erso ns w ith a w ell-d o cum ented histo ry o f p rio r im m unizatio n w ere assum ed to be v accinated . All o f them had receiv ed a live, attenuated m easles v accine.
A histo ry o f exp o sure to m easles w as d efined as a kno w n co ntact w ith a case 8 to 18 days befo re the o nset o f the d isease.
S t a t is t ic a l a n a ly s is . Frequency distributio ns w ere analysed by the chi-square test and the d ifferences co nsid ered significant at the 0.05 level.
RESULTS
During the stud y p erio d 290 p atients o ut o f a to tal o f 293 no tified cases w ere co nsid ered as having clinical m easles after review ing by the Health D ep artm ent o f the Municipality o f N iteró i. The m ajo rity o f susp ected cases (250 - 86.2% ) w ere inv estigated by ep id em io lo gists or nurses o f the D ep artm ent o f Health to co llect info rm atio n acco rd ing to the questio nnaire d esig ned fo r this study. O nly investig ated cases w ere includ ed in this analysis.
The m ed ian ag e w as 11 years (range, 5 m o nths to 31 y ears) and 76.0 % o f the cases
w ere in the scho o l-ag e child ren (5 to 19 years o f age). Patients > 1 0 years o f ag e acco unted fo r 60.0 % o f all stud ied cases (Table 1).
T a b le 1 - D is t r ib u t io n b y a g e a n d s e x o f 2 5 0 m e as le s c as e s in v e s t ig at e d i n t h e M u n ic ip alit y o f N it e r ó i\ S t at e o f R io d e Ja n e i r o .
Nr % A ge distributio n by age gro ups (years)
< 1 18 7.2
1 - 4 30 12.0
5 - 9 52 20.8
10 - 14 96 38.4
15 - 19 42 16.8
> 20 12 4.8
Sex
male 113 45.2
female 137 54.8
E x p o s u r e h is t o r ie s . A histo ry o f exp o sure to m easles w as p resent in 149 (59-6% ) patients. The m o st freq u ently rep o rted sites o f transmissio n w ere: scho o l: 67 (45.0% ) cases; ho m e: 47 (31-5% ) cases; neig hbo urho o d : 24 (16.1% ) cases and o thers: 11 (7.4% ) cases. Setting o f transm issio n varied acco rd ing to age. The m o st frequently rep o rted co ntacts fo r child ren < 5 y ears o f ag e w ere the ho m e and neighbo urho o d , and am o ng p atients fro m 5 to 19 years o f ag e, scho o l and ho m e. The relatio n scho o l/ ho m e increased acco rd ing to age.
V a c c i n a t i o n s t at u s . Vaccinatio n status w as kno w n fo r 127 (50.8% ) stud ied cases and 97 (76.4% ) o f them had b een v accinated befo re their first birthday. The o ther 30 (23.6% ) p atients had receiv ed m easles v accine o n o r after o ne y ear o f age (14 cases receiv ed o ne d o se and l6 cases receiv ed tw o o r m o re d o ses). All the child ren < 1 y ear o f ag e w ere unv accinated . The rem aining 123 p atients w ere unv accinated o r had a p o o r d o cum ented histo ry o f prio r v accinatio n.
C o m p l i c a t i o n s o f m e as le s . O ne o r m o re co m p licatio ns w ere rep o rted fo r 68 (27.2% ) cases, includ ing p neum o nia in 37 (54.4% ), otitis med ia in 22 (32.4% ), d iarrhea in 12 (17.7% ), and o thers (sinusitis, laryngitis, to nsilitis) in 8 (11.8% ). No case o f encep halitis w as seen. Freq u ency o f co m p licatio ns varied acco rd ing to each ag e gro up stud ied (Table 2). They w ere m o re co m m o nly enco u ntered am o ng child ren < 1 y ear o f ag e and tho se o f the ag e gro up fro m 15 to 19 years o ld . A to tal o f 22 (8.9% ) ho sp italizatio ns w ere required by m easles co m p licatio ns.
Oliveira SA, Soares WN, Dalston MO, A lmeida MTGN, Costa AJL. Clinical and epidemiological findings during a measles outbreak o ccuring in a populaticm with a high vaccination coverage. Revista da Sociedade Brasileira de M edicina Tropical 28:339- 343, out- dez, 1995.
Frequency o f co m p licatio ns also varied acco rd ing to p revio us v accinatio n status (Table 3). They w ere se en m o re freq u ently in u nv accinated cases (33.3% ) than in tho se v accinated (21.3% ). This result w as statistically significant (x 2: 4.60 - P < 0.05). The relatio n b etw een co m p licatio ns and histo ry o f previo us v accinatio n w ere also analy sed w itho ut includ ing child ren < 1 y ear o f ag e (Table 4). A ltho ugh they co ntinued to b e seen mo re frequently in unv accinated cases (29.5% ) than in tho se v accinated (21.3% ), this result w as no t statistically significant anym o re (x 2: 2.09 - P > 0.05).
D ISCU SSIO N
In the USA, fro m 1984 to 1988, 58% o f rep o rted cases affected child ren >10 years o f age, co m p ared w ith 10% d uring the p erio d I960 to 19643. This p ro gressiv e upw ard shift in the ag e d istributio n o f m easles incid ence to w ard s o ld er child ren has b een rep o rted by fo reign autho rs6 8 20, and also in o ur co untry513. This fact w as co nfirm ed in this w o rk, w here the m ed ian ag e fo r the p erio d stud ied w as 11 years. The p ro p o rtio n o f cases am o ng child ren fro m 10 to 14 years o f ag e (38.4 % ) exceed ed the o ne am o ng child ren fro m 1 to 4 and fro m
5 to 9 years o ld to g ether (32.8% ). Furthermo re, the p ro p o rtio n o f cases am o ng p eo p le fro m 15 to 19 years o ld (16.8% ) w as hig her than the p ro p o rtio n fo und in child ren fro m 1 to 4 years o ld (12.0% ), the ag e g ro up o f hig hest incid ence befo re the beg inning o f v accinatio n campaigns5.
The chang es in the age d istributio n o f m easles in c id e n c e c an b e relate d to so m e facto rs: a) Becau se o f the mass cam p aign v a c c in a tio n , th e n u m b e r o f s u s c e p tib le child ren und er the ag e o f 5 d ecreased and the m easles cases that o ccu r in ad o lescents and ad ults cam e to rep resent a great p ercentag e o f all rep o rted cases2, b ) The d ecrease o f m easles transm issio n in the co m m unity caused by
v ac c in atio n also p ro te c te d in d ire c tly
unv accinated p eo p le (herd immunity). So , many o f them b ecam e o ld er w itho ut having co ntact w ith the m easles virus, either natural o r by v accinatio n219.
A no ther facto r that can b e resp o nsible fo r the chang es o f m easles ep id em io lo g y is that v accine ind uced immunity can w ane w ith
tim e11. Krug m an10 b eliev es that w aning
im m unity may b e insig nificant fro m the ep id em io lo gic p o int o f v iew and that ad equate immunizatio n is sufficient to p ro tect m o re then 95% o f the v accinated child ren o v er a lo ng perio d.
Ho w ever, the increase o f m easles cases in p rev io usly v accinated child ren has b een
d escribed by d ifferent autho rs6 7 11 21 n. The
reaso ns o f v accine failure can b e related to: neutralizatio n o f v accine virus by maternal antibo d ies o r tho se artificially ad m inistered (gamma g lo bulin)15 20; im p ro p er sto rage o r hand ling v accine lead ing to inactiv atio n o f live virus9 16 17; “primary v accine failure”, w hich o ccurs in abo ut 5% o f v accines18.
In Brazil, b ecau se o f the high incid ence o f m easles at a yo ung age, ro utine m easles v accine has b een reco m m end ed fo r child ren 9 m o nths o f age o r o ld er since 1982. As 13-15% o f the child ren remain suscep tible w ith this strategy, a few States d ecid ed to ad m inister a seco nd d o se o f the v accine after 15 m o nths o f ag e13. N ev ertheless, this p o licy w as no t ad o p ted fo r the co untry as a w ho le, lead ing to insufficient lev els o f v accine co v erag e to attain d isease co ntro l.
O liv e ir a SA , S o ar e s W N, D als t o n M O , A lm e i d a M TG N , C o s t a A JL. C l in ic al a n d e p id e m i o l o g i c a l f i n d i n g s d u r in g a m e as le s o u t b r e a k o c c u r in g in a p o p u la t i o n w it h a h ig h v a c c in a t io n c o v e r ag e . R e v is t a d a S o c i e d a d e B r a s ile ir a d e M e d ic in a T r o p ic al 2 8 : 3 3 9 - 3 4 3 , o u t - d e z , 1 9 9 5 .
birthd ay. The o ther 30 (23.6% ) p atients had receiv ed m easles v accine at o r after o ne year o f ag e. The hig h p ercentag es o f p eo p le v accinated w ith o nly o ne d o se befo re their first
birthd ay co u ld exp lain v accine failure.
M o reo v er, alteratio ns in m easles v accine quality co uld also have co ntributed to the results related abo v e. O liveira et al., in 198616 and in 199017, carried o u t an inv estigatio n to ev aluate the basic p ro ced ures inv o lv ed in the sto rage o f m easles v accine in p ublic health units o f the M unicip ality studied. The first research sho w ed that all v accine sam p le titers w ere w ell b elo w the m inim al reco m m end ed p o tency by the m anufacters. Fo ur years later, d esp ite the im p ro v em ent o f the co ld chain w hen co m p ared to the fo rm er evaluatio n, 55.2% o f the v accine sam p les w ere still und er the m inim al reco m m end ed p o tency.
Transm issio n in scho o ls acco unted fo r 67 (45-0% ) o f 149 cases w ith a histo ry o f m easles, fo llo w ed by ho m es (47 cases 31-5% ) o r neig hbo urho o d (24 cases - 16.1% ). Mo reo ver, transm issio n in scho o ls w as m o re frequent fo r p eo p le fro m 5 - 1 9 years o f age. The highest p ro p o rtio n in these settings can b e exp lained b ec au se stud ents transm it infectio n m o re efficiently than y o u ng er child ren. They frequently visit o ther classro o m s and attend so cial ev ents o utsid e the scho o l, w hich bring large gro up s to gether6. It w as particularly interesting to o bserv e that transm issio n in m ed ical settings (ho sp itals, em erg ency ro o ms, and p hy sicians’ o ffices), fo und in o nly o ne case in this study, had no t so m uch im p o rtance as the o ne o bserv ed by M anso n et al.12 and A tkinso n et al1 in the USA , in 18.9% and 18.4% o f their cases, respectiv ely.
D e s p ite th e h ig h p e r c e n ta g e o f co m p licatio ns (27.8% ) v erified d uring the p erio d studied , no case o f d eath caused by m easles w as rep o rted . Furthermo re, no case o f m easles - asso ciated d eath has b een no tified to Niteró i Health D ep artm ent since 1987, w hich is acco rd ing to the high lev els o f v accinatio n co v erag e o btained o v er the last years, mainly in child ren und er 5 years o ld 5. As it w as exp ected , co m p licatio ns w ere m o re co m m o nly enco untered am o ng child ren und er 1 y ear o f ag e (55.6% ), but high rates w ere also fo und in o ther ag e gro up s. In sp ite o f these high rates o nly 8.9% o f the p atients w ere ho sp italized w ith o ne o r m o re co m p licatio ns o f the d isease. The ho sp italizatio n rates fo und here are w ell
lo w er than tho se verified b y M anso n et al.12 and A tkinso n et al1 in the USA, 44.3% and 26.4% o f their cases, resp ectiv ely. The less severe m easles cases o bserv ed are p ro bably due to the chang e in the ag e d istributio n and the increasing m ed ian ag e o f rep o rted cases. The histo ry o f previo us v accinatio n did no t d iminish the num ber o f co m p licatio ns o f the cases studied.
The results o f this study sho w chang es in
the ep id em io lo g y o f m easles in the
M unicip ality o f N iteró i, mainly in the last three y ears. A ll the facts h ere d iscussed , as v accinatio n strategies ad o p ted and causes o f v accine failures, may hav e co ntributed to these results. Therefo re, to attain m easles co ntro l it is impo rtant to co ntinue the effo rts to increase v accinatio n co v erage, and to exp and active surveillance o f the d isease.
RESUMO
No perío do de março de 1991 a abril de 1992, 2 5 0 casos de um total de 2 9 3 no tificados co mo sarampo em Niterói, RJ fo ram estudado s. Em 75,9% dos casos o sarampo o co rreu em pessoas de idade esco lar ( m ediana: 11). História de expo sição estava p res m t e em 1 4 9 pacientes. O lo cal de transmissão v ariou de aco rdo co m a idade sendo a esco la o mais freqüent em ent e enco iitrado (45% ). Em 1 2 7 casos o estado v acinai era co nhecido e 76,4% deles tinham sido v acinado s antes do prim eiro aniv ersário. Em 6 8 caso s um a o u mais co mplicaçõ es estav am presentes e em 8,9% deles a hospitalização fo i necessária. Co mplicações fo ram mais freqüent es em meno res de um ano de idade (55,6% ). História de v acinação prév ia não dim inuiu o núm ero de complicaçõ es dos casos estudados. Os resultado s d e s t e t ra b a l h o m o s t ra m m u d a n ç a s n a epidemio lo gia do sarampo , co m alteraçõ es na distribuição etária dos casos da do ença, leim ido ã o co iTência de importantes surtos da virose entre ado lecentes e adultos jo v ens.
Palav ras- chav es: Epidemio lo gia do sarampo . Falha de v acinação . Co mplicaçõ es do sarampo .
A CKNOWLEDGEMENT
This w o rk w o uld no t b e p o ssible w itho ut the aid o f the health w o rkers fro m the M unicip ality o f N iteró i, State o f Rio d e Janeiro .
REFERENCES
1. A tkinson W L, H adley SC, Redd SB, O renstein WA. M easles Surveillance - U nited States. 19 9 1 .
O liv e ir a SA , S o ar e s W N, D als t o n M O , A lm e i d a M TG N , C o s t a A JL. C l in i c al a n d e p i d e m i o l o g i c a l f m d i n g s d u r in g a m e as le s o u t b r e a k o c c u r in g m a p o p u l a t i o n w it h a h ig h v a c c in a t io n c o v e r ag e . R e v is t a d a S o c i e d a d e B r a s ile ir a d e M e d ic in a T r o p ic al 2 8 : 3 3 9 - 3 4 3 , o u t - d e z , 1 9 9 5 .
M orbidity and M ortality W eekly Report 41:1-12, 1992.
2. Barata PCR, Leal M C. D istrib uição etária do
saram po e vacinação: considerações sob re alguns dados do M unicípio do Rio de Janeiro. Cadernos de Saúde Pública 1 :5 0 - 5 7 ,1 9 8 5 .
3. C enters for D iseases Control. US Public H ealth Service. M easles surveillance rep ort no. 1 1 ,1 9 7 7 -1981. A tlanta, G eorgia, 1982.
4. C en ters . for D iseases C ontrol. M easles;
W ashington, 19 9 0 . M orbidity and M ortality W eekly Report 3 9 :4 7 3 - 6 ,1 9 9 0 .
5. Fund ação M unicipal d e Saúde d e N iterói.
S up erintendência de A çõ es de Saúde.
D epartam ento de Epidemiologia e C ontrole de A gravos. Inform e Epidem iológico Sarampo p .l -8 ,1 9 9 2 .
6 . G u s taf so n T L, L iev en s AW , B ru n e l l PA ,
M o ellen b erg RG, Buttery CMG, Schulster LM. M easles outbreak in a fully immunized secondary - school population. T he N ew England Journal of M edicine 3 1 6 :7 7 1 - 7 7 4 ,1 9 8 7 .
7. Judelsohn R, Fleissner ML, O ’ M ara DJ. School
-based m easles outbreaks: Correlations of age at imm unization w ith risk o f disease. A m erican
Journal Public H ealth 7 0 :1 1 6 2 - 1 1 6 5 ,1 9 8 0 .
8. K rause PJ, C herry JD , D eseda-Tous J, Champion JG , Strassburg M , Sullivan C, Spencer MJ, Bryson YJ, W elliver RC, Boyer KM. Epidem ic measles in
young adults. A nnals o f Internal M edicine 90:873-8 7 6 ,1 9 7 9 .
9. K rugm an KD, M eyer BC, Parkman PD, W ittle JJ, M eyer HM . Im po tency o f live - virus vaccines as a
result o f im proper handling in clinical practice. T he Journal of Pediatrics 9 1 :5 1 2 - 5 1 4 ,1 9 7 4 .
10. K rugm an S. Present status o f measles and rubella immunization in the U nited States. A m edical
progress report. The Journal o f Pediatrics 78:1, 1971.
11. Linnem an njr C C ,RotteT C , Schiff G M ,YoutseyJL.
A seroepidem iologic study o f a m easles epidem ic in a highly imm unized population. A m erican Journal o f Epidem iology 9 5 :2 3 8 - 2 4 6 ,1 9 7 2 .
12. M anson W H , Ross LA, Lanson J, W right Jr HT. Epidem ic m easles in th e p o stv accin e era:
evaluation o f epidemiology, clinical presentation and com plications during an urban outbreak.The
Pediatric Infectious D isease Journal 12:42- 48, 1993.
13. M inistério da Saúde. Fund ação N acional de Saúde. C apacitação de Pessoal para a V igilância E p i d e m i o l ó g i c a d o S a ra m p o . M ó d u l o Institucional I. Brasília p . 1 - 7 7 ,1 9 9 2
14. N agy G, K ósa S,Takátsy S, Roller M .The use o f IgM tests for analysis of the cause of m easles failures: exp erience gained in an epidem ic in H ungary in 1 9 8 0 and 1981.Jou rn al o f M edical V irology
13:93-1 0 3 ,13:93-1 9 8 4 .
15- O liveira SA, H om m a A , Camillo-Coura L, Loureiro MLR A lmeida M TGN. A ntimeasles antibodies in ch ildren sub m itted to different v accin atio n schedules. Revista da Sociedade Brasileira de M edicina Tropical 2 6 :7 7 - 8 2 ,1 9 9 3 .
16. O liveira SA, H om m a A , M ahul D C, Loureiro MLR Camillo-Coura L. A valiação das co n d içõ es de esto cag em da vacina co n tra o saram po nas unidades sanitárias dos M unicípios de N iterói e São G onçalo - Estado do Rio de Janeiro. Revista do Instituto de M edicina Tropical de São Paulo 3 3 :3 1 3 - 3 1 8 ,1 9 9 1 .
17. O liveira SA, Loureiro MLR Kiffer CRX M aduro LMF. Re-evaluation o f th e b asic p ro ced u res involved in the storage of m easles v accin e in public health units o f th e M unicipality o f N iterói, State o f Rio de Janeiro, Brazil. Revista da Sociedade Brasileira de M edicina Tropical 26:145-1 4 9 ,26:145-1 9 9 3 .
18. Plotkin SA. Failures of pro tectio n b y m easles vaccine. The Journal o f Pediatrics 8 2 :908- 911, 1973.
19. Schaffner W, Schlederberg AES, Byrne EB. Clinical epidem iology of sporadic m easles in a highly immunized population.The N ew England Journal o f M edicine 2 7 9 :7 8 3 - 7 8 9 ,1 9 6 8 .
20. Shasby M, Shope TC, D ow ns H, H errm ann KL, Polkow ski J. Ep idem ic m easles in a highly vaccinated population.T he N ew England Journal o f M edicine 296:585- 589, 1977.
21. Smith FR, CurranA S, RacitiA K , Black FL. Reported m easles in perso n immunologically prim ed by p rio r v accin atio n . T h e Jo u rn al o f Ped iatrics 9 0 :3 9 1 - 3 9 3 ,1 9 8 2 .
22. W yll SA, W itte JJ. M easles in previously vaccinated children. A n epidem iological study.The Journal o f A m erican M edical A ssociation 2 1 6 :1 3 0 6 - 1 3 1 0 ,
